Demyelinating diseases of central or peripheral origin are diseases which destroy myelin which is a substance compounded principally of fats and proteins. It is wrapped in numerous thin layers around nerve fibers where it acts as an insulator and speeds the transmission of messages along the nerve fibers. These afflictions include for example MS, GuillainBarre syndrome and polymyositis. Of these, MS is by far the most prevalent. This invention will be described principally as it relates to MS.
MS is a disease of profound suffering and pervasive disability, the etiology of which remains unknown despite intensive investigation. It consists of patches or plaques of damaged myelin scattered throughout the central nervous system resulting from demyelination and subsequent scar formation. The name "multiple sclerosis" describes the fact that in this disease there are many damaged areas filled with sclerotic (scar) tissue. Over a long period, new scar tissue may develop or old ones enlarge. The result is progressive degeneration of the nervous system resulting in progressive debilitation of the afflicted individual.
MS significantly affects the most productive human age group (20-40 yrs). There are close to a million victims in the United States alone. The chief consequence of the disease is increasing deterioration of neurological function. Most victims are confined to wheelchairs or bed after 10 yea:s. The prevalence ranges from 50/100,000 in the United States to 200/100,000 in Canada, Northern Great Britain, parts of France, Scandinavia and Russia.
In the absence of a known cause for the disease, treatments have been empirical. The treatments can be divided principally into anti-inflammatory, immunosuppressive, anti-infective and biological response modifications. Additionally, a large number of miscellaneous treatments have been attempted. No satisfactory treatment of MS has yet been revealed.
ACTH has been of some benefit in promoting remission of acute attacks, but has not been shown to modify the overall course of the disease. Combination therapy with ACTH and cyclophosphamide have shown some promise in temporarily halting the progression of severe MS. However, the work is very recent, and no final conclusion has been possible.
Copolymer-I, a synthetic polypeptide resembling myelin basic protein has shown some benefit, but these results are also too recent for proper evaluation.
In 1982 the National Multiple Sclerosis Society published a booklet entitled Therapeutic Claims in Multiple Sclerosis (International Standard Book Number 0-9608098-0-5). In it more than twenty methods of treating MS ranging from diet control to a wide variety of therapeutic agents including, for example, anticoagulants, vasodilators, immunosuppressants, and protease inhibitors are discussed. The majority are characterized as ineffective, not recommended, or not sufficiently tested.
There is a need for a safe, reliable and effective method of treating MS and related diseases so as to retard their progression, particularly a treatment which will retard demyelination before the disease becomes disabling. It would be especially convenient if treatment could be accomplished by way of sustained release compositions which would decrease the number of separate dosage units required each day during treatment, thus improving compliance.
Colchicine is (S)-N-(5,6,7,9-tetrahydro-9-oxabenzo [a]heptaten-7-yl) acetamide. It has long been known as a therapeutic agent for humans, particularly as a gout suppressant and in the treatment of Familial Mediterranean Fever. It may be safely administered both orally and parenterally. Its activity in the mammalian body is well known and understood. Colchiceine is the 10- demethylated homolog of colchicine. It has also been used for the same purposes. Colchicine is the preferred therapeutic agent for the known utilities. It is also the preferred agent for use in this invention because it is readily available at reasonable cost and is extremely effective in retarding the progression of MS.